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Bacteriophages effectively counteract diverse bacterial infections, and their ability to treat most types of cancer has been explored using phage engineering or phage-virus hybrid platforms. In the present study, it was demonstrated that the bacteriophage MS2 can affect the expression of genes associated with the proliferation and survival of LNCaP prostate epithelial cells. LNCaP cells were exposed to bacteriophage MS2 at a concentration of 1×10 7 plaque forming units/ml for 24-48 h. After exposure, various cellular parameters, including cell viability, morphology, and changes in gene expression, were examined. MS2 affected cell viability adversely, reducing viability by 25% in the first 4 h of treatment; however, cell viability recovered within 24-48 h. Similarly, the AKT , androgen receptor, integrin α5, integrin β1, MAPK1, MAPK3, STAT3 , and peroxisome proliferator-activated receptor-γ coactivator 1α genes, which are involved in various normal cellular processes and tumor progression, were significantly upregulated, whereas the expression levels of HSP90, ITGB5, ITGB3, HSP27, ITGAV , and PI3K genes were unchanged. Therefore, based on viability and gene expression changes, bacteriophage MS2 severely impaired LNCaP cells by reducing anchorage-dependent survival and androgen signaling. A caveolin-mediated endocytosis mechanism for MS2-mediated signaling in prostate cancer cells was proposed based on reports involving bacteriophages T4, M13, and MS2, and their interactions with LNCaP and PC3 cell lines., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Sanmukh et al.)

Gestational diabetes mellitus (GDM) plus rectus abdominis muscle (RAM) myopathy predicts long-term urinary incontinence (UI). Atrophic and stiff RAM are characteristics of diabetes-induced myopathy (DiM) in pregnant rats. This study aimed to determine whether swimming exercise (SE) has a therapeutic effect in mild hyperglycemic pregnant rats model. We hypothesized that SE training might help to reverse RAM DiM. Mild hyperglycemic pregnant rats model was obtained by a unique subcutaneous injection of 100 mg/kg streptozotocin (diabetic group) or citrate buffer (non-diabetic group) on the first day of life in Wistar female newborns. At 90 days of life, the rats are mated and randomly allocated to remain sedentary or subjected to a SE protocol. The SE protocol started at gestational day 0 and consisted of 60 min/day for 6 days/week in a period of 20 days in a swim tunnel. On day 21, rats were sacrificed, and RAM was collected and studied by picrosirius red, immunohistochemistry, and transmission electron microscopy. The SE protocol increased the fiber area and diameter, and the slow-twitch and fast-twitch fiber area and diameter in the diabetic exercised group, a finding was also seen in control sedentary animals. There was a decreased type I collagen but not type III collagen area and showed a similar type I/type III ratio compared with the control sedentary group. In conclusion, SE during pregnancy reversed the RAM DiM in pregnant rats. These findings may be a potential protocol to consider in patients with RAM damage caused by GDM., (© 2022. The Author(s).)

Wild-type or engineered bacteriophages have been reported as therapeutic agents in the treatment of several types of diseases, including cancer. They might be used either as naked phages or as carriers of antitumor molecules. Here, we evaluate the role of bacteriophages M13 and T4 in modulating the expression of genes related to cell adhesion, growth, and survival in the androgen-responsive LNCaP prostatic adenocarcinoma-derived epithelial cell line. LNCaP cells were exposed to either bacteriophage M13 or T4 at a concentration of 1 × 10 5 pfu/mL, 1 × 10 6 pfu/mL, and 1 × 10 7 pfu/mL for 24, 48, and 72 h. After exposure, cells were processed for general morphology, cell viability assay, and gene expression analyses. Neither M13 nor T4 exposure altered cellular morphology, but both decreased the MTT reduction capacity of LNCaP cells at different times of treatment. In addition, genes AKT , ITGA5 , ITGB1 , ITGB3 , ITGB5 , MAPK3 , and PI3K were significantly up-regulated, whilst the genes AR , HSPB1 , ITGAV , and PGC1A were down-regulated. Our results show that bacteriophage M13 and T4 interact with LNCaP cells and effectively promote gene expression changes related to anchorage-dependent survival and androgen signaling. In conclusion, phage therapy may increase the response of PCa treatment with PI3K/AKT pathway inhibitors.

Recent evidence suggests that aerobic physical training may attenuate the deleterious effects of cancer risk factors, including smoking. We investigated the effects of cigarette smoke inhalation and aerobic physical training on the expression of steroid receptors and inflammatory and apoptotic proteins in the prostate. Forty male Wistar rats were distributed in four groups: control (CO), exercise (EXE), cigarette smoke exposure (CS), and cigarette smoke exposure with exercise (CS+EXE). For eight weeks, animals were repeatedly exposed to cigarette smoke for 30 min or performed aerobic physical training either with or without the cigarette smoke inhalation protocol. Following these experiments, we analyzed prostate epithelial morphology and prostatic expression of androgen (AR) and glucocorticoid receptors (GR), insulin-like growth factor (IGF-1), B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) via immunohistochemistry. Cigarette smoke exposure stimulated the expression of AR, IGF-1, BCL-2, and NF-κB while downregulating BAX, IL-6, and TNF-α labeling in the prostate. In contrast, aerobic physical training attenuated cigarette smoke-induced changes in AR, GR, IGF-1, BCL-2, IL-6, TNF-α, and NF-κB. This suggests that cigarette smoke stimulates inflammation and reduces apoptosis, culminating in increased prostatic epithelial and extracellular matrices, whereas physical training promoted beneficial effects towards maintaining normal prostate morphology and protein levels.

Stroke is a serious complication of sickle cell anemia (SCA) affecting children and adults. Recent reports suggested that tumor necrosis factor-α (TNF-α) (-308) polymorphism is an important risk factor for stroke in children with SCA. The role of TNF-α polymorphism in the frequency of brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) abnormalities in adults with SCA is still uncertain. Our objective was to evaluate the frequency of TNF-α polymorphism in adults with SCA and to correlate it to brain MRI and MRA findings. TNF-α (-308) polymorphism was determined in 49 adults with SCA. All subjects were evaluated with brain MRI/MRA to establish the presence of intracranial abnormalities. Thirty-three (67.3%) had abnormal brain MRA scans, 8 (16.3%) had intracranial stenosis and 29 (59.2%) showed arterial tortuosity. Forty-one (83.7%) had the GG genotype and 8 had the GA genotype. There was no correlation between homozygosity for G allele and MRA or MRI abnormalities. Although TNF-α (-308) polymorphism is a potential predictor of the genetic risk for stroke in children, we found no association between the polymorphism and large vessel abnormalities in adults with SCA., (Copyright © 2010 S. Karger AG, Basel.)

The influence of a nonsoluble beta-1,3-glucan preparation on the immune response of mice and rats to sheep red blood cells and to phytohemagglutinin A (PHA) T cell mitogen were evaluated. Treatment with glucan increased the hemagglutinin titers in both species and the response of mice spleen cells to PHA.